3D Echocardiography - A Useful Method for Cardiovascular Risk Assessment in End-Stage Renal Disease Patients.

Patients with chronic kidney disease (CKD) have an increased risk of premature mortality, mainly due to cardiovascular causes. The association between hemodialysis and accelerated atherosclerosis has long been described. The ankle-brachial index (ABI) is a surrogate marker of atherosclerosis and recent studies indicate its utility as a predictor of future cardiovascular disease and all-cause mortality. The clinical implications of ABI cut-points are not well defined in patients with CKD. Echocardiography is the most widely used imaging method for cardiac evaluation. Structural and functional myocardial abnormalities are common in patients with CKD due to pressure and volume overload as well as non-hemodynamic factors associated with CKD. Our study aimed to identify markers of subclinical cardiovascular risk assessed using ABI and 2D and 3D echocardiographic parameters evaluating left ventricular (LV) structure and function in patients with end-stage renal disease (ESRD) (patients undergoing dialysis), patients after kidney transplantation and non-ESRD patients (control). In ESRD, particularly in hemodialysis patients, changes in cardiac structure, rather than function, seems to be more pronounced. 3D echocardiography appears to be more sensitive than 2D echocardiography in the assessment of myocardial structure and function in CKD patients. Particularly 3D derived end-diastolic volume and 3D derived LV mass indexed for body surface appears to deteriorate in dialyzed and transplanted patients. In 2D echocardiography, myocardial mass represented by left ventricular mass/body surface area index (LVMI) appears to be a more sensitive marker of cardiac structural changes, compared to relative wall thickness (RWT), left ventricle and diastolic diameter index (LVEDDI) and left atrial volume index (LAVI). We observed a generally favorable impact of kidney transplantation on cardiac structure and function; however, the differences were non-significant. The improvement seems to be more pronounced in cardiac function parameters, peak early diastolic velocity/average peak early diastolic velocity of mitral valve annulus (E/e´), 3D left ventricle ejection fraction (LV EF) and global longitudinal strain (GLS). We conclude that ABI is not an appropriate screening test to determine the cardiovascular risk in patients with ESRD.

3D Echocardiography - A Useful Method for Cardiovascular Risk Assessment in End-Stage Renal Disease Patients.

Patients with chronic kidney disease (CKD) have an increased risk of premature mortality, mainly due to cardiovascular causes. The association between hemodialysis and accelerated atherosclerosis has long been described. The ankle-brachial index (ABI) is a surrogate marker of atherosclerosis and recent studies indicate its utility as a predictor of future cardiovascular disease and all-cause mortality. The clinical implications of ABI cut-points are not well defined in patients with CKD. Echocardiography is the most widely used imaging method for cardiac evaluation. Structural and functional myocardial abnormalities are common in patients with CKD due to pressure and volume overload as well as non-hemodynamic factors associated with CKD. Our study aimed to identify markers of subclinical cardiovascular risk assessed using ABI and 2D and 3D echocardiographic parameters evaluating left ventricular (LV) structure and function in patients with end-stage renal disease (ESRD) (patients undergoing dialysis), patients after kidney transplantation and non-ESRD patients (control). In ESRD, particularly in hemodialysis patients, changes in cardiac structure, rather than function, seems to be more pronounced. 3D echocardiography appears to be more sensitive than 2D echocardiography in the assessment of myocardial structure and function in CKD patients. Particularly 3D derived end-diastolic volume and 3D derived LV mass indexed for body surface appears to deteriorate in dialyzed and transplanted patients. In 2D echocardiography, myocardial mass represented by left ventricular mass/body surface area index (LVMI) appears to be a more sensitive marker of cardiac structural changes, compared to relative wall thickness (RWT), left ventricle and diastolic diameter index (LVEDDI) and left atrial volume index (LAVI). We observed a generally favorable impact of kidney transplantation on cardiac structure and function; however, the differences were non-significant. The improvement seems to be more pronounced in cardiac function parameters, peak early diastolic velocity/average peak early diastolic velocity of mitral valve annulus (E/e´), 3D left ventricle ejection fraction (LV EF) and global longitudinal strain (GLS). We conclude that ABI is not an appropriate screening test to determine the cardiovascular risk in patients with ESRD.

Treatment of lower extremity superficial vein thrombosis with low molecular weight heparin.

AIM: The aim of our study was to ascertain the efficacy of low-molecular-weight heparin (LMWH) in the treatment of patients with SVT. MATERIAL AND METHODS: A group of 336 outpatients with clinical diagnosis of SVT was evaluated in this prospective study. At the beginning of the study all patients were examined by clinical investigation, laboratory tests and duplex ultrasound investigation (examination). All patients included into the study were treated with LMWH. Clinical and ultrasound evaluation was carried out on days 10, 30 and 90 of the follow-up. This clinical study of SVT treatment with LMWH was organized in 18 outpatient departments in the Slovak Republic. RESULTS: After 10 days of treatment with LMWH in full therapeutic dosage, an improvement in the clinical symptoms was demonstrated in 93 % of patients; a complete resolution of clinical symptoms was demonstrated in 4 % of patients. On day 30 (after 10 days of LMWH treatment in full therapeutic dosage and further treatment in halved therapeutic dosage up to 20 days) a complete resolution of clinical symptoms was observed in 59 % (n = 189) of patients. Patients were further clinically evaluated on day 90, after two months of no anticoagulation treatment. The clinical evaluation revealed a complete resolution of symptoms in 88 % (n = 283) of patients and improvement in symptoms in 11.6 % (n = 34). Two patients developed pulmonary embolization; extension of SVT was seen in one patient and SVT recurrence in two patients. CONCLUSION: Superficial vein thrombosis can propagate into the deep veins with the risk of pulmonary embolism. The results indicate that current ambulatory treatment regimen using LMWH in the treatment of SVT is effective and safe (Fig. 4, Ref. 30).

Consensus Document on Intermittent Claudication from the Central European Vascular Forum (C.E.V.F.)-3rd revision (2013) with the sharing of the Mediterranean League of Angiology and Vascular Surgery, and the North Africa and Middle East Chapter of International Union of Angiology.

This paper is the review of the Consensus Document on Intermittent Claudication of the Central European Vascular Forum (CEVF), published in 2008, and and shared with the North Africa and Middle East Chapter of International Union of Angiology and the Mediterranean League of Angiology and Vascular Surgery. The Document presents suggestions for general practitioners and vascular specialists for more precise and appropriate management of PAD, particularly of intermittent claudication, and underlines the investigations that should be required by GPs and what the GP should expect from the vascular specialist (angiologist, vascular surgeon). The idea of the Faculty is to produce a short document, which is an easy reference in daily clinical practice, both for the GPs and vascular specialists.

Duplex ultrasound, clinical score, thrombotic risk, and D-dimer testing for evidence based diagnosis and management of deep vein thrombosis and alternative diagnoses in the primary care setting and outpatient ward.

Deep vein thrombosis (DVT) has an annual incidence of 0.2% in the urban population. First episodes of calf vein thrombosis (CVT) and proximal DVT are frequently elicited by risk factors, including varicose veins, cancer, pregnancy/postpartum, oral contraceptives below the age of 50 years, immobility or surgery. Leg pain and tenderness in the calf and popliteal fossa on physical examination may result from other conditions than DVT labeled as alternative diagnosis (AD) Congenital venous thrombophilia is present in every third first DVT, increased FVIII in every fourth first DVT, and FV Leiden/FII mutation in 40% of women on oral anticonceptive pill before reaching the menopause. Routine thrombophilia testing for FV Leiden/prothrombin mutation and FVIII as main risk factor for venous thrombosis is recommended. Primary superficial venous thrombosis (SVT) and DVT patients with a autosomal dominant family history of DVT are candidates for thrombophilia testing for congenital AT, PC and PS deficiency. The requirement for a safe diagnostic strategy of CVT and DVT should be based on an objective post-test incidence of venous thromboembolism (VTE) of less than 0.1% with a negative predictive value for exclusion of DVT of 99.9% during 3 months follow-up. Modification of the Wells score by elimination of the "minus 2 points" for AD is mandatory and will improve the diagnostic accuracy of CVT/DVT suspicion in the primary care setting and outpatient ward. The sequential use of complete DUS, ELISA D-dimer testing and modified clinical Wells' score assessment is safe and effective for the exclusion and diagnosis of CVT, DVT and AD. About 10% to 20% of patients with DVT develop overt post-thrombotic syndrome (PTS) at one year post-DVT, and both PTS and DVT recurrences further increase to about 30% during long-term follow-up. Objective risk stratification of PTS complications using DUS for recanalization and reflux and D-dimer testing will become an integral part in routine clinical practice to assess the optimal duration of wearing medical elastic stockings and anticoagulation for the prevention DVT recurrence as the best option to reduce the incidence and costs of suffering from irreversible PTS.

Cancer as a risk factor for residual pulmonary embolism.

AIM: Despite anticoagulation in some patients after pulmonary embolism (PE) pulmonary emboli are not completely resolved. The goal of our prospective study was to evaluate the rate of residual pulmonary emboli in repeated CT pulmoangiography 13-17 weeks after setting the diagnosis of PE and to determine the relationship between primary risk factors for PE, the results of the primary entry tests and the incidence of residual pulmonary embolism. METHODS: Fifty-three patients aged 59.8 (54.9-67.7) years with confirmed first episode of PE were enrolled into the study, 37 patients after appropriate anticoagulation underwent the repeated CT pulmoangiography. RESULTS: This examination confirmed the presence of embolic residues in pulmonary arteries in 8 patients (21.6%). After analyzing the observed entry (by admission to the hospital with the diagnosis of PE) parameters (age, sex, systolic and diastolic blood pressure, heart rate, waist circumference, body weight, body mass index, presence of hypertension, diabetes mellitus type 2, the presence of inflammatory disease, immobilization, recent surgery or overcome trauma, history of malignancy, venous thromboembolism in the past, previous treatment with statins, CRP, troponin T, TSH, D-dimer, total cholesterol, LDL cholesterol, HDL cholesterol, serum trigylcerides) the authors note that the only parameter that was significantly associated with persisting embolic residues was malignancy (2/29 patients without residues vs. 4/8 patients with residues, odds ratio=13.5, 95%CI=1.8344-99.35, P=0.0106). There was no statistically significant difference in other observed parameters. CONCLUSION: Malingnancy represents an important predictor of incomplete recanalization of pulmonary arteries after the first episode of pulmonary embolism.

Nitric oxide synthases in varicose vein wall.

INTRODUCTION: Venous wall weakness is supposed to be the most probable reason of primary varicosis. There are conflicting findings in literature about its structural changes. NO is potent vasodilatator due to the smooth muscle relaxation. It is synthesized by nitric oxide synthase (NOS). There are 3 known isoforms of NOS: nNOS (neuronal NOS), iNOS (inducible NOS), eNOS (endothelial NOS). MATERIAL AND METHODS: 10 varicose vein and 10 control vein samples were processed by standard light microscopy method. Sections were then processed by standard immuno-histochemic technique using rabbit polyclonal antibodies against all 3 NOS isoforms: iNOS, eNOS (SantaCruz, USA), nNOS (BioScience, USA). Antibodies expression was evaluated semiquantitatively and then proved morphometricaly by 2D image analysis (ImageJ 1.34n, National Institute of Health, USA). Total area of NOS isoforms expressions was determined by color analysis and color digital substraction. RESULTS: Histomorphological and semi quantitative evaluation of NOS isoforms showed discontinuous and significantly lower expression of all 3 NOS isoforms in tunica media of varicose veins compared with control group, where the expression of all 3 NOS isoforms was continuous. For the statistical analysis unpaired t-test was used. DISCUSSION AND CONCLUSION: Our results suppose lower NO levels in varicose vein wall, deducing that varicose vasodilatation is due to other mechanism, although the stage of chronic venous disease of varicose vein samples was undetermined. Our results are in contradiction with previously published results of Howlader et al., who observed raised total NO levels in patients with severe stages of chronic venous disease(Tab. 2, Fig. 13, Ref. 18).

[Is our management of patients with claudicatio intermittens correct?]. / Liecime správne pacientov s claudicatio intermittens?

Claudicatio intermittens is the major symptom of peripheral arterial disease of extremities. At the same time it is an important manifestation of systemic atherosclerosis. In spite of the fact that the diagnosis of claudicatio intermittens requires only simple, non-invasive, and inexpensive diagnostic methods, the disease is still underdiagnosed and often goes untreated. Proper treatment of patients with claudicatio intermittens prevents the progression of the disease and development of critical limb ischemia as well as reduces other complications of systemic atherosclerosis, including cardiovascular death.

Cryoglobulinemia manifested by gangraene of almost all fingers and toes.

Cryoglobulinemia is a rather rare condition accompanying quite a broad spectrum of different states and diseases. Mixed or polyclonal cryoglobulins can be seen in patients with autoimmune disorders, chronic infections and lymphoproliferative disorders. Monoclonal cryoglobulins are often revealed in patients with multiple myeloma or Waldenström's macroglobulinemia. Cryoglobulinemia is in most cases asymptomatic. Cryoglobulinemic vasculitis is an immune complex-mediated systemic disorder involving mostly small, but sometimes also larger vessels. In this report, we describe a case of a patient presented with gangrene of almost all fingers and toes, who was finally diagnosed and treated as cryoglobulinemic vasculitis due to multiple myeloma.

[Superficial thrombophlebitis--diagnostics and treatment]. / Povrchová tromboflebitída--diagnostika a liecba.

Superficial thrombophlebitis (ST) is a common disease, usually considered benign. However, the practice of systemic duplex ultrasonography has revealed a large number of deep-vein thromboses concomitant with ST. In contrast with extensive information on the management of deep vein thrombosis, little is known about the most appropriate treatment of the ST. Systematic duplex ultrasonography investigation has been proposed in the initial management of ST, to detect the presence of any underlying deep vein thrombosis. Because ST may extend into the deep venous system and potentially engender pulmonary embolism, treatment with low-molecular-weight-heparins might be the best choice. In our work diagnostic and therapeutic procedures for ST, proposed by Slovak angiological society, Slovak society for vascular surgeons, Slovak dermatological society, Slovak society for haemostasis and thrombosis, Slovak surgical society and Slovak internistic society are discussed.

Comparison of collagen subtype I and III presence in varicose and non-varicose vein walls.

STUDY OBJECTIVES: The connective tissue alterations in varicose vein wall are supposed to be one of the main causes of primary varicose vein (main sign of human lower limbs chronic venous insufficency). METHODS: 5 varicose vein samples from 5 patients undergoing stripping surgery of long saphenous vein were compared with 5 control samples of healthy (non-dilated) long saphenous veins from necroptic material (with no history of varicosis). They were fixed in a Baker solution, processed by use of light microscopic method, cut to ultra-thin sections (4-5 microm) and stained with PicroSirius Red for collagen. Sections were scanned with light microscope (Leica, Germany) and camera Canon S50 (Germany) and analysed by morphometric programme Image J v.1.38g (National Institute of Health, USA). RESULTS: In the group of healthy (non-dilated) veins the mean collagen I/III ratio value was 31.40 and in the group of varicose veins the mean collagen I/III ratio was 12.35; the difference is statistically significant: healthy veins contain significantly more of collagen subtype I and varicose veins contain significantly more of collagen subtype III in their walls. CONCLUSION: The statistically significant difference in the collagen I/III ratio between the groups of healthy (non-dilated) and varicose (dilated) vein walls is worthy of further following (Tab. 2, Fig. 7, Ref. 12). Full Text (Free, PDF) www.bmj.sk.

[Peripheral arterial disease of extremities--guidelines for diagnostic and treatment]. / Odporúcania pre diagnostiku a liecbu periférneho artériového ochorenia koncatín (PAO).

Diagnostic and therapeutic guidelines of peripheral arterial disease of extremities recommanded by five scientific societies of Slovak Medical Association (Slovak Angiological Society, Slovak Society for Vascular Surgery, Slovak Cardiologic Society, Slovak Internal Society and Slovak Radiologic Society) are discussed in this article. Peripheral arterial disease (PAO) of extremities is an important manifestation of systemic atherosclerosis The lower the ankle-brachial pressure index, the greater the risk of serious cardiovascular events (e.g. myocardial infarction, stroke). Nevertheless, patients with PAO are undertreated with regard to use of antiplatelet drugs or lipid-lowering drugs, as compared with patients with coronary artery disease.

Inflammation--a lifelong companion. Attempt at a non-analytical holistic view.

Inflammation is a key component of the immune system. It has important functions in both defense and pathophysiological events maintaining the dynamic homeostasis of a host organism including its tissues, organs and individual cells. On the cellular level it is controlled by more than 400 currently known genes. Their polymorphisms and environmental conditions give rise to different genotypes in human population. Pro-inflammatory genotype, which dominates in the present population, may be advantageous in childhood but not in elderly people because it is characterized by an increased vulnerability to, and intensity of, inflammatory reactions. These reactions may be the possible reasons of chronic inflammatory diseases, especially in old age. Better understanding of complex molecular and cellular inflammatory mechanisms is indispensable for detailed knowledge of pathogenesis of many diseases, their prevention and directed drug therapy. Here we summarize the basic current knowledge on these mechanisms.

[Polymyalgia rheumatica and giant cell arteritis--first results of a year-long study]. / Polymyalgia rheumatica a obrovskobunková arteritída: prvé výsledky rocného sledovania.

INTRODUCTION: Due to ageing of population, gerontorheumatology becomes more and more important. Both polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) typically develop in later life and they have many other common features. The aim of our study was to explore diagnostic and prognostic markers and, prospectively, establish diagnostic and therapeutic algorithm for patients with PMR and GCA. SAMPLE AND METHODS: We examined 27 patients with suspected PMR or OBA. The diagnosis was verified in 22 patients. Three of them were in a long-term clinical remission. Besides examination for basic clinical and laboratory parameters, all other patients were subjected to ultrasonography of temporal artery and peripheral joints to detect any exudates. Also, they were examined for T-cell subpopulations in peripheral blood and HLA antigens. RESULTS: Exudate was confirmed in 7 patients; some of them had exudate in multiple joints. Puncture of synovial fluid was done in 4 patients. Increased resistance index of temporal artery was found in 2 patients with GCA and 4 patients with PMR. GCA patients showed lower level of T-cells and increased activation of CD8-cells. Decreased count of CD8+ T-cells was observed in 56 % of PMR patients. Analysis of HLA antigens indicates that GCA, rheumatoid arthritis and, probably, PMR are associated with HLA-DR4 antigen in Slovak population. CONCLUSION: The importance of assessment of disease activity and its prognosis in PMR or GCA patients via ultrasonographic evaluation of exudate in peripheral joints and resistance index of temporal artery as well as the analysis of T-cell distribution in peripheral blood and incidence of HLA-antigens has not been proved yet. Practical significance of monitoring the above-mentioned parameters can be verified only by further prospective study performed with a larger sample of patients.

Efficacy of a 6-month treatment with Daflon 500 mg in patients with venous leg ulcers associated with chronic venous insufficiency.

AIM: Epidemiological data show that standard compression therapy for leg ulceration in chronic venous insufficiency (CVI) often fails to effectively improve patients' condition. This study assesses the contribution of Daflon 500 mg added to conventional therapy in the healing of hypostatic ulcers of CVI patients. METHODS: Patients of about 65 years were included, with ulcers > or = 2 and > or = 10 cm diameter on 1 or 2 limbs, Doppler ankle/arm pressure index > 0.9, and no recent history of skin graft. Controls (n=68) remained on compression alone while the tested group (n=82) also received Daflon 500 mg 2 tablets/day during 6 months. Treatment could be stopped as soon as the reference ulcer appeared fully healed. Primary endpoints were the rate of healed ulcers and the time to complete healing assessed by planimetry/photography and clinical examination. Variations of the ulcer surface, appearance of the skin, and clinical symptoms of CVI were the secondary criteria. RESULTS: Only 7% of Daflon 500 mg patients necessitated the full 6 month therapy. Whatever the lesion size, from W8 significantly more healed ulcers were observed under Daflon 500 mg (p=0.004), and the ulcer surface was more reduced (p=0.012). For large ulcers, the rate of healing was approximately 2-fold higher with Daflon 500 mg, and the percentage of ulcers healed before W24 was significantly higher (p=0.008). Heavy leg sensation was significantly improved by Daflon 500 mg from W4 (p < 0.05). No treatment-related side effects were reported and the acceptability was considered excellent by 85% of Daflon 500 mg patients. CONCLUSION: Six months of Daflon 500 mg in addition to compression significantly improve some clinical symptoms and accelerate the healing process in patients with ulcerous complications of CVI, with a good acceptability.

Inflammatory mechanisms involving neutrophils in chronic venous insufficiency of lower limbs.

BACKGROUND: It is supposed that an inflammatory reaction is one of the major factors responsible for the chronic venous insufficiency (CVI) of lower limbs which cause leg ulcers. OBJECTIVES: The main objective of the present study was to determine the differences in the levels of typical inflammatory mediators and markers produced by neutrophils of patients with CVI and normal control subjects. SUBJECTS AND METHODS: 26 patients with CVI and 39 clinically healthy subjects were included in the study. In peripheral neutrophils of both groups the production of superoxide, total reactive oxygen intermediates and activities of lysosomal enzymes were measured together with the expression of 8 adhesion molecules. RESULTS: Increased formation of superoxide by patient neutrophils and activities of elastase in both neutrophils and serum of patients were demonstrated. On the contrary, activities of myeloperoxidase and beta-D-glucuronidase were decreased in patient neutrophils. Comparing to control group adhesion molecules CD11b, CD18, CD31, CD49d, CD54 and CD62L were increased on the surface of patient neutrophils whereas no differences were observed in the expression of CD11a abd CD15. CONCLUSION: The neutrophils of patients with CVI are primed and/or activated because they are able to release higher amount of superoxide, lysosomal enzymes and express elevated number of adhesion molecules. It may serve as one of the important evidences of an inflammatory mechanism involved in the pathogenesis of chronic venous insufficiency. (Tab. 3, Ref. 27.)